When Steroids Cause Psychosis

One adverse effect that has been seen with selective serotonin reuptake inhibitors (SSRIs), especially in the elderly patients, is the development of SIADH; there is also some literature associating SSRIs with increased falls as well as literature suggesting an association between SSRI use and osteoporotic fracture risk. Lastly, patients should not discontinue medications abruptly and need to be counseled about symptoms of discontinuation syndrome. Even in light of these cautions, in the instance of corticosteroid-induced depressive symptoms, there is support in the literature for the use of SSRIs. In choosing an SSRI, paroxetine and fluoxetine are most likely to have significant drug–drug interactions through the cytochrome P450 iso-enzyme family, particularly 2D6 and 3A4. Sertraline, citalopram, and escitalopram do not significantly induce or inhibit cytochrome P450 activity.

The literature raises specific concern about possible adverse effects of tricyclic antidepressants (TCAs), with observations of symptom exacerbation in patients with corticosteroid-induced psychosis treated with TCAs. For this reason, TCAs are not recommended for use in steroid-induced mood symptomatology.

Anticonvulsants

Published studies of anticonvulsants including phenytoin, levetiracetam, and lamotrigine have not demonstrated benefit from the use of these agents in preventing corticosteroid-induced psychosis.10-12 Case reports exist supporting the use of lamotrigine and gabapentin.^35,36 However, lamotrigine may be difficult to use because it must be started at a very low dose and titrated slowly over weeks to months to the target dose. The use of gabapentin in psychiatric disorders, particularly bipolar disorder, has not been shown to be effective.³⁷

Summary and Recommendations

Establishing a treatment algorithm (see Figure 2, p. 41) for corticosteroid-induced psychosis is difficult given the lack of high-quality prospective trials. However, most case reports describe benefit from atypical antipsychotics and lithium. With appropriate monitoring, a low-dose atypical antipsychotic such as olanzapine, risperidone, or quetiapine can be helpful in alleviating symptoms of steroid-induced psychosis. In select patients without renal insufficiency or the need for diuretic, ACE inhibitors, or NSAID therapy, lithium may be used but requires careful monitoring and vigilance for signs of toxicity. When patients cannot tolerate atypical antipsychotics or lithium, valproic acid or carbamazepine with appropriate monitoring may be useful alternatives. SSRIs may be helpful in patients with depressive symptomatology without a history of mania, but there is some evidence that tricyclic antidepressants may exacerbate the symptoms.